Submissions for variant NM_004975.4(KCNB1):c.1700G>A (p.Ser567Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003749576	SCV004490411	uncertain significance	Developmental and epileptic encephalopathy, 26	2023-04-09	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 567 of the KCNB1 protein (p.Ser567Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNB1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNB1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV004736370	SCV005341637	uncertain significance	KCNB1-related disorder	2024-04-02	no assertion criteria provided	clinical testing	The KCNB1 c.1700G>A variant is predicted to result in the amino acid substitution p.Ser567Asn. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.